Publications by authors named "Evangelos Kalaitzakis"

117 Publications

Curriculum for ERCP and endoscopic ultrasound training in Europe: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement.

Endoscopy 2021 10 26;53(10):1071-1087. Epub 2021 Jul 26.

Department of Gastroenterology and Hepatology, University Hospitals Leuven, and TARGID, KU Leuven, Leuven, Belgium.

The European Society of Gastrointestinal Endoscopy (ESGE) has recognized the need to formalize and enhance training in endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS). This manuscript represents the outcome of a formal Delphi process resulting in an official Position Statement of the ESGE and provides a framework to develop and maintain skills in ERCP and EUS. This curriculum is set out in terms of the prerequisites prior to training; recommended steps of training to a defined syllabus; the quality of training; and how competence should be defined and evidenced before independent practice. 1: Trainees should be competent in gastroscopy prior to commencing training. Formal training courses and the use of simulation in training are recommended. 2: Trainees should keep a contemporaneous logbook of their procedures, including key performance indicators and the degree of independence. Structured formative assessment is encouraged to enhance feedback. There should be a summative assessment process prior to commencing independent practice to ensure there is robust evidence of competence. This evidence should include a review of a trainee's procedure volume and current performance measures. A period of mentoring is strongly recommended in the early stages of independent practice. 3: Specifically for ERCP, all trainees should be competent up to Schutz level 2 complexity (management of distal biliary strictures and stones > 10 mm), with advanced ERCP requiring a further period of training. Prior to independent practice, ESGE recommends that a trainee can evidence a procedure volume of > 300 cases, a native papilla cannulation rate of ≥ 80 % (90 % after a period of mentored independent practice), complete stones clearance of ≥ 85 %, and successful stenting of distal biliary strictures of ≥ 90 % (90 % and 95 % respectively after a mentored period of independent practice). 4: The progression of EUS training and competence attainment should start from diagnostic EUS and then proceed to basic therapeutic EUS, and finally to advanced therapeutic EUS. Before independent practice, ESGE recommends that a trainee can evidence a procedure volume of > 250 cases (75 fine-needle aspirations/biopsies [FNA/FNBs]), satisfactory visualization of key anatomical landmarks in ≥ 90 % of cases, and an FNA/FNB accuracy rate of ≥ 85 %. ESGE recognizes the often inadequate quality of the evidence and the need for further studies pertaining to training in advanced endoscopy, particularly in relation to therapeutic EUS.
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http://dx.doi.org/10.1055/a-1537-8999DOI Listing
October 2021

Osteoclast: like giant cell undiferrentiated pancreatic tumor diagnosed by means of EUS guided FNA.

Acta Biomed 2021 05 12;92(2):e2021106. Epub 2021 May 12.

University of Crete, Medical Faculty, Department of Gastrenterology.

Objective: Osteoclast-like giant cell tumours are rare abdominal malignant neoplasms mainly arising in the pancreas. Because of their rarity, clinical and cytopathology reports are very limited, and sonographic features have not been clearly specified ; these tumors are easily misdiagnosed by ultrasound as mucinous cystic tumors (MCTs)  or solid pseudopapillary neoplasms (SPNs).

Case Study: We report a case of osteoclast  like giant cell tumor arising in the pancreas of an 80 year old female patient offered by EUS-FNA cytology on direct and cell block slides. A biphasic pattern composed by a malignant mononuclear cell component and a giant cell component were hallmarks to the diagnosis.

Conclusion: Our case highlights the performance of EUS-FNA in the diagnostic approach of  abdominal tumours and the significance of cell block method in the interpretation of osteoclast-like giant cell pancreatic tumour.
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http://dx.doi.org/10.23750/abm.v92i2.9482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182582PMC
May 2021

Echogenic Surface Enhancements for Improving Needle Visualization in Ultrasound: A PRISMA Systematic Review.

J Ultrasound Med 2021 Apr 18. Epub 2021 Apr 18.

Gastrounit, Herlev University Hospital, Herlev, Denmark.

Optimal visualization of needles in clinical ultrasound imaging is important and challenging, especially at steep angles. Improvement of visualization has been attempted with various techniques, for example, coatings and dimples. This systematic review summarizes enhancement techniques and identifies superior echogenic surface enhancements. Twenty-four papers were identified providing visibility measures for 33 different echogenic needles. These were grouped according to surface characteristics and ranked. Echogenic needles ranked higher than standard needles especially at steeper angles. Among the echogenic needles, coated needles were seemingly better visualized "in vivo" than noncoated needles, despite heterogeneity in study conditions. No unambiguous comparison revealed which needle was best visualized.
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http://dx.doi.org/10.1002/jum.15713DOI Listing
April 2021

Bacterial infections in acute pancreatitis.

Eur J Gastroenterol Hepatol 2021 04;33(4):599-600

Department of Gastrointestinal and Liver Diseases, Copenhagen University Hospital Herlev, University of Copenhagen, Copenhagen, Denmark.

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http://dx.doi.org/10.1097/MEG.0000000000002124DOI Listing
April 2021

Recent advances in the treatment of primary sclerosing cholangitis.

Expert Rev Gastroenterol Hepatol 2021 Apr 14;15(4):413-425. Epub 2020 Dec 14.

Department of Internal Medicine, University Hospital Heraklion, Faculty of Medicine, University of Crete, Rethymno, Greece.

: PSC is a rare liver disease that leads frequently to cirrhosis and need for liver transplantation. No medical treatment is of proven value. Liver transplantation is the only curative therapy available. There is a big medical need to find medical therapy that can alter the natural history of the disease.: The authors highlight advances in PSC, based on recent literature retrieved from PubMed until September 2020 regarding both medical and endoscopic biliary therapy.Future possibilities for treatment of PSC are discussed.: Biliary endoscopy is the cornerstone in the treatment of dominant strictures. Single-user peroral cholangioscopy is an emerging modality. Balloon dilatation therapy is the treatment of choice of dominant strictures. The most promising medical therapies showing efficacy in phase II trials are nor-Ursodeoxycholic acid, obethicolic acid, the non-steroidal FXR agonist Cilofexor and Aldafermin, a synthetic analogue of FGF-19. Antibiotics, particularly vancomycin have shown potential benefits, particularly in children but phase III studies are lacking. In observational studies of effects of biological therapy in patients with IBD/PSC adalimumab was associated with reduction in ALP. Results of liver transplantation are favorable but recurrence can be of clinical relevance particularly in patients transplanted before the age of 40.
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http://dx.doi.org/10.1080/17474124.2021.1860751DOI Listing
April 2021

Diagnosis and immunocytochemical characterization of an EBV related diffuse B large cell lymphoma of the retroperitoneum from cell block preparations obtained by means of EUS guided FNA.

Rev Esp Enferm Dig 2021 Jun;113(6):470-471

Gastroenterology, Medical Faculty. University of Crete.

Diffuse large B cell lymphoma (DLBCL) in the retroperitoneum has been scarcely reported and the diagnostic workup is challenging due to difficulties in access to tissue. A 73-year-old female presented to the gastroenterology clinic, with recent-onset atypical abdominal pain and alternating constipation and diarrhea.
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http://dx.doi.org/10.17235/reed.2020.7247/2020DOI Listing
June 2021

An international, multi-institution survey on performing EUS-FNA and fine needle biopsy.

Endosc Ultrasound 2020 Sep-Oct;9(5):319-328

Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.

Background And Objectives: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) and fine needle biopsy (FNB) are effective techniques that are widely used for tissue acquisition. However, it remains unclear how to obtain high-quality specimens. Therefore, we conducted a survey of EUS-FNA and FNB techniques to determine practice patterns worldwide and to develop strong recommendations based on the experience of experts in the field.

Methods: This was a worldwide multi-institutional survey among members of the International Society of EUS Task Force (ISEUS-TF). The survey was administered by E-mail through the SurveyMonkey website. In some cases, percentage agreement with some statements was calculated; in others, the options with the greatest numbers of responses were summarized. Another questionnaire about the level of recommendation was designed to assess the respondents' answers.

Results: ISEUS-TF members developed a questionnaire containing 17 questions that was sent to 53 experts. Thirty-five experts completed the survey within the specified period. Among them, 40% and 54.3% performed 50-200 and more than 200 EUS sampling procedures annually, respectively. Some practice patterns regarding FNA/FNB were recommended.

Conclusion: This is the first worldwide survey of EUS-FNA and FNB practice patterns. The results showed wide variations in practice patterns. Randomized studies are urgently needed to establish the best approach for optimizing the FNA/FNB procedures.
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http://dx.doi.org/10.4103/eus.eus_56_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811723PMC
September 2020

Clinical impact of endoscopic ultrasound-guided through-the-needle microbiopsy in patients with pancreatic cysts.

Endoscopy 2021 Jan 21;53(1):44-52. Epub 2020 Jul 21.

Gastroenterology Unit, Division of Endoscopy, Herlev Hospital, Herlev, Denmark.

Background: The limited data on the utility of endoscopic ultrasound (EUS)-guided through-the-needle biopsies (TTNBs) in patients with pancreatic cystic lesions (PCLs) originate mainly from retrospective studies. Our aim was to determine the clinical impact of TTNBs, their added diagnostic value, and the adverse event rate in a prospective setting.

Methods: This was a prospective, single-center, open-label controlled study. Between February 2018 and August 2019, consecutive patients presenting with a PCL of 15 mm or more and referred for EUS were included. Primary outcome was a change in clinical management of PCLs following TTNB compared with cross-sectional imaging and cytology. Adverse events were defined according to the ASGE lexicon.

Results: 101 patients were included. TTNBs led to a change in clinical management in 11.9 % of cases (n = 12). Of these, 10 had serous cysts and surveillance was discontinued, while one of the remaining two cases underwent surgery following diagnosis of a mucinous cystic neoplasm. The diagnostic yield of TTNBs for a specific cyst diagnosis was higher compared with FNA cytology (69.3 % vs. 20.8 %, respectively;  < 0.001). The adverse event rate was 9.9 % (n = 10; 95 % confidence interval 5.4 % - 17.3 %), with the most common event being acute pancreatitis (n = 9). Four of the observed adverse events were severe, including one fatal outcome.

Conclusions: TTNBs resulted in a change of clinical management in about one in every 10 patients; however, the associated adverse event risk was substantial. Further studies are warranted to elucidate in which subgroups of patients the clinical benefit outweighs the risks.
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http://dx.doi.org/10.1055/a-1214-6043DOI Listing
January 2021

Extrapancreatic infections are common in acute pancreatitis and they are related to organ failure: a population-based study.

Eur J Gastroenterol Hepatol 2020 10;32(10):1293-1300

Digestive Disease Center, Copenhagen University Hospital/Herlev, University of Copenhagen, Copenhagen, Denmark.

Background: Although the impact of pancreatic infections in acute pancreatitis has been studied extensively, there are no population-based data on extrapancreatic infections and their potential relation to organ failure. We aimed to study the occurrence of pancreatic and extrapancreatic bacterial infections in acute pancreatitis and their relation to patient outcome.

Patients And Methods: All patients with first-time acute pancreatitis from 2003 to 2012 in a defined area in Sweden were retrospectively evaluated. Data on acute pancreatitis severity, organ failure, infections, and in-hospital mortality were collected.

Results: Overall, 304 bacterial infections occurred in 248/1457 patients (17%). Fifteen percent had extrapancreatic and 2% had pancreatic infections. The lungs (35%), the urinary tract (24%), and the bile ducts (18%) were the most common sites of extrapancreatic infections. Organ failure, severe acute pancreatitis, and in-hospital mortality were more common in patients with vs those without (pancreatic/extrapancreatic) infections (P < 0.05). Organ failure and severe acute pancreatitis occurred more frequently in pancreatic vs extrapancreatic infections (70% vs 34%, P < 0.001 and 67% vs 28%, P < 0.001), but in-hospital mortality did not differ between the two groups (7.4% vs 6.8%, P = 1.0). Both pancreatic and extrapancreatic infections were independent predictors of organ failure (P < 0.05). Out of culture-positive infections, 18% were due to antibiotic-resistant bacteria, without any significant difference between extrapancreatic vs pancreatic infections (P > 0.05). About two out of five infections were of nosocomial origin.

Conclusion: Extrapancreatic infections occurred in 15% and pancreatic infections in 2% of patients with first-time acute pancreatitis. Both pancreatic and extrapancreatic infections were independent predictors of organ failure, leading to increased mortality.
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http://dx.doi.org/10.1097/MEG.0000000000001847DOI Listing
October 2020

EUS-guided through-the-needle microbiopsy of pancreatic cysts: Technical aspects (with video).

Endosc Ultrasound 2020 Jul-Aug;9(4):220-224

Gastroenterology Unit, Division of Endoscopy, Herlev and Gentofte Hospital, Copenhagen University, Herlev, Denmark.

Pancreatic cystic lesions are frequently encountered and diagnostically challenging as some of the cysts may have malignant potential (mucinous) while others are completely benign (serous). EUS-guided through-the-needle biopsy (EUS-TTNB) of the cyst wall has recently been introduced as an alternative to cyst fluid cytology. Several studies have shown that microbiopsies outperform cytology in terms of distinction between mucinous and nonmucinous lesions, but also in determining the specific cyst diagnosis. However, little is known about the technical aspects of tissue sampling with TTNB. Herein, we summarize our experience with the procedure in a tertiary referral center and discuss indications, technical aspects, and safety of the procedure. Most adverse events (AEs) associated with the procedure are mild, but there is emerging evidence that the rate of postprocedural pancreatitis is higher compared to standard fine-needle aspiration. The added diagnostic yield should therefore be placed in perspective with an increased risk of AEs. Prospective studies are warranted to fully identify which patient groups could benefit from EUS-TTNB.
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http://dx.doi.org/10.4103/eus.eus_12_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529000PMC
July 2020

Patient reported exposure to smoking and alcohol abuse are associated with pain and other complications in patients with chronic pancreatitis.

Pancreatology 2020 Jul 11;20(5):844-851. Epub 2020 May 11.

Department of Clinical Medicine, University of Bergen, Bergen, Norway; Medical Department, Haukeland University Hospital, Bergen, Norway.

Background/objectives: Smoking and alcohol abuse are established risk factors for chronic pancreatitis (CP). Few studies have examined how exposure to smoking and alcohol abuse act as risk factors for complications in CP. Our aim was to examine associations between patient reported exposure to smoking and alcohol abuse and complications in CP in a large cohort of patients from the Scandinavian and Baltic countries.

Methods: We retrieved data on demographics, CP related complications and patients' histories of exposure to smoking and alcohol abuse from the Scandinavian Baltic Pancreatic Club database. Associations were investigated by univariate and multivariate logistic regression analyses. Results are presented as odds ratios (OR) with 95% confidence intervals.

Results: A complete history of smoking and alcohol exposure was available for 932 patients. In multivariate regression analyses, the presence of pain and exocrine pancreatic insufficiency were both significantly associated with history of smoking (OR 1.94 (1.40-2.68), p < 0.001 and OR 1.89 (1.36-2.62), p < 0.001, respectively) and alcohol abuse (OR 1.66 (1.21-2.26), p = 0.001 and 1.55 (1.14-2.11), p = 0.005, respectively). Smoking was associated with calcifications (OR 2.89 (2.09-3.96), p < 0.001), moderate to severe ductal changes (OR 1.42 (1.05-1.92), p = 0.02), and underweight (OR 4.73 (2.23-10.02), p < 0.001). History of alcohol abuse was associated with pseudocysts (OR 1.38 (1.00-1.90) p = 0.05) and diabetes mellitus (OR 1.44 (1.03-2.01), p = 0.03). There were significantly increased odds-ratios for several complications with increasing exposure to smoking and alcohol abuse.

Conclusion: Smoking and alcohol abuse are both independently associated with development of complications in patients with CP. There seems to be a dose-dependent relationship between smoking and alcohol abuse and complications in CP.
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http://dx.doi.org/10.1016/j.pan.2020.05.001DOI Listing
July 2020

Endoscopic ultrasound-guided gastro-enteric anastomosis: A systematic review and meta-analysis.

Dig Liver Dis 2020 11 3;52(11):1294-1301. Epub 2020 Jun 3.

Gastro Unit, Division of Endoscopy, Copenhagen University Hospital Herlev, Denmark.

Background And Aims: Endoscopic ultrasound-guided gastro-enteric anastomosis (EUS-GEA) using lumen-apposing metal stents (LAMS) is emerging as a minimally invasive alternative to surgery across several indications. Literature on this subject is heterogeneous, with variable reporting of techniques and outcomes. Our aim was to perform a meta-analysis of published data on EUS-GEA, providing a pooled estimate of technical and clinical outcomes.

Methods: The protocol was registered in PROSPERO (Reg. no. CRD42018111110). PubMed, Embase, Scopus, and Web of Science databases were searched until February 2019 for studies describing patients undergoing EUS guided enteric anastomosis. PRISMA methodology was used. Pooled technical and clinical success rates as well as pooled adverse events rates were calculated. Study quality, publication bias, and heterogeneity were explored.

Results: Twelve studies including 290 patients were included, published between 2016 and 2019. All studies but one were retrospective. Main procedure indication was gastric outlet obstruction (62.4%), followed by ERCP access (27.9%) in patients with gastric bypass surgery. Direct puncture technique was the most frequently adopted (68.2%). Pooled technical success rate (12 studies, 290 patients) was 93.5% [95% confidence interval (CI) 89.7-6.0%; I:0%], while clinical success rate (11 studies, 260 patients) was 90.1% [95%CI 85.5-93.4%; I:0%]. Pooled total adverse events rate (11 cohorts, 261 patients) was 11.7% [95%CI 8.2-16.6%; I:0%], mainly mild/moderate: 10.6% [95%CI 7 - 15.6%]. No publication bias or significant heterogeneity was found.

Conclusions: EUS-GEA has a high rate of technical and clinical success when performed in expert centers. The procedure appears to be relatively safe, and might represent a non-inferior minimally invasive alternative to surgery. The paucity of long-term clinical outcomes suggests prudency and need for further research, especially regarding non-malignant indications.
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http://dx.doi.org/10.1016/j.dld.2020.04.021DOI Listing
November 2020

Increase in the incidence of alcoholic pancreatitis and alcoholic liver disease in Iceland: impact of alcohol consumption.

Scand J Gastroenterol 2020 May 14;55(5):615-620. Epub 2020 Apr 14.

Department of Gastroenterology, Landspitali University Hospital, Reykjavik, Iceland.

To analyze the incidence of acute alcoholic pancreatitis and of severe alcoholic liver disease (ALD) and its association with alcohol consumption with identification of both alcoholic cirrhosis (AC) and severe alcoholic hepatitis (AH), in a population-based setting. A search was undertaken in diagnoses database for diagnostic codes in order to find patients hospitalized with incident acute alcoholic pancreatitis (AP) and alcoholic liver disease in Iceland in 2001-2015. Diagnoses were verified in all patients who were retrospectively reviewed. Those with ALD had either AC or AH. Alcohol sales during the study period were obtained from Statistics Iceland. Overall, 273 patients with acute AP, mean age at diagnosis 50 (14) years, 74% males and 159 patients with ALD, mean age 57 (11) years, 73% males, were identified. Mean alcohol consumption was 6.95 (0.4) liters and increased by 21% over the study period. The annual incidence of AP increased from 4.2 per 100.000 to 9.5 and ALD from 1.6 to 6.1 per 100.000. Trend analysis showed a significant annual increase of 7% (RR 1.07, 95%CI 1.04-1.10) for AP and an annual increase of 10.5% (RR 1.10, 95%CI 1.06-1.15) for ALD. The increase was only significant in males. Increase alcohol consumption over a 15 year study period was associated with an increase in the incidence of severe alcoholic liver disease and alcohol-related acute pancreatitis in males but not in females.
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http://dx.doi.org/10.1080/00365521.2020.1751874DOI Listing
May 2020

Abstinence from alcohol and alcohol rehabilitation therapy in alcoholic liver disease: a population-based study.

Scand J Gastroenterol 2020 Apr 1;55(4):472-478. Epub 2020 Apr 1.

Digestive Disease Center, Copenhagen University Hospital/Herlev, University of Copenhagen, Copenhagen, Denmark.

Abstinence from alcohol is recommended in patients diagnosed with alcoholic hepatitis (AH) and alcoholic cirrhosis (AC). We aimed to determine the impact of alcohol abstinence on prognosis of patients with AC and AH. All incident AC and AH patients in Iceland 2001-2016 were identified. Cirrhosis was confirmed clinically, biochemically, with imaging and histologically. Abstinence, alcohol rehabilitation and survival were analyzed. Overall, 169 patients with AC and/or AH were identified. Eleven died during index hospitalization, leaving 158 patients for final analysis, median (IQR) age 56 years (48-65), 72% males. Over all 61 patients (39%) had AC, 40 (25%) AH and 57 (36%) features of both. Thirty-nine percent of patients remained abstinent during follow-up and 63% underwent alcohol rehabilitation. Moderate to severe ascites at diagnosis (odds ratio (OR): 3.05, 95% confidence interval (CI): 1.37-7.02) and lack of alcoholic rehabilitation (OR: 5.28, 95% CI: 2.24- 14.11) were independent predictors of abstinence. Abstinence at one year of follow-up was not related to increased survival. Patients surviving one year, abstinence during follow-up was related to increased survival for both groups. Abstinence from alcohol following AC/AH diagnosis was achieved in 39% of patients. Abstinence was not related to increased survival for alcoholic liver disease patients at one-year, which might partly indicate that this might be a marker that some patients were 'too sick to drink'. AC and AH patients who survived one year and remained abstinent had a favorable long-term prognosis.
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http://dx.doi.org/10.1080/00365521.2020.1743751DOI Listing
April 2020

Multiple risk factors for diabetes mellitus in patients with chronic pancreatitis: A multicentre study of 1117 cases.

United European Gastroenterol J 2020 05 17;8(4):453-461. Epub 2020 Jan 17.

Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark.

Background: Diabetes mellitus is a common complication of chronic pancreatitis. It is traditionally considered to develop as a consequence of beta cell loss, but there might be additional factors. Recent studies have highlighted the importance of type 2 diabetes-related risk factors in this context and population-based studies show increased risk of diabetes following acute pancreatitis. The aim of this study was to explore multiple risk factors for diabetes in patients with chronic pancreatitis.

Methods: We conducted a multicentre, cross-sectional study of patients with definitive chronic pancreatitis according to the M-ANNHEIM criteria. We used multivariable logistic regression models to determine risk factors independently associated with diabetes.

Results: The study included 1117 patients of whom 457 (40.9 %) had diabetes. The mean age was 52.8 ± 14.2 years and 67% were men. On multivariate analysis, parameters indicative of beta cell loss (pancreatic calcification, exocrine insufficiency, pancreatic resection) were confirmed as independent risk factors for diabetes (all  ≤ 0.02). In addition, type 2 diabetes-related risk factors (dyslipidaemia and overweight/obesity) were associated with the presence of diabetes (all  ≤ 0.002). Patients with a history of pancreatic fluid collections (indicative of previous attacks of acute pancreatitis) had a marginally increased risk of diabetes ( = 0.07).

Conclusion: In patients with chronic pancreatitis the presence of diabetes is associated with multiple risk factors including type 2 diabetes-related factors. Our observations attest to the understanding of this entity and may have implications for treatment.
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http://dx.doi.org/10.1177/2050640620901973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226693PMC
May 2020

Osteoporosis in cirrhotics before and after liver transplantation: relation with malnutrition and inflammatory status.

Scand J Gastroenterol 2020 Mar 17;55(3):354-361. Epub 2020 Mar 17.

Department of Orthopaedics and Clinical Sciences, Lund University, Skane University Hospital, Malmö, Sweden.

Liver cirrhosis is associated with osteoporosis and liver transplantation (LT) with increased bone loss. This study aimed to in LT candidates investigate the potential relation between bone mineral density (BMD) and BMD loss in those who undergo LT, with malnutrition, systemic inflammation, and hormonal status. We included 102 consecutively recruited cirrhotic LT candidates between May 2004 and April 2007. BMD was assessed by means of dual energy X-ray absorptiometry (DXA). Malnutrition was defined by means of anthropometry and assessment of recent weight loss. In 75/102 patients, serum-thyroid stimulating hormone (TSH), free triiodthyronine (T3) and free thyroxine (T4) and growth hormone (GH), cortisol, free testosterone, dehydroepiandrosterone sulfate, estradiol, interleukin-6, and tumor necrosis factor (TNF)-α was assessed. Overall 57/102 patients received a LT and 47/102 were followed for one year post-LT. At follow-up, nutritional status and BMD were assessed in all patients ( = 47) while 34/47 had available blood samples for analysis. Forty (40%) LT- candidates had osteopenia or osteoporosis and 34 (38%) were malnourished. Malnutrition was associated with osteopenia/osteoporosis (odds ratio: 3.5, 95% CI 1.4, 9.9). Hip BMD Z-score decreased -0.25 (95% CI -0.41, -0.09) from baseline to one year post-LT. High baseline TNF-α correlated with a more marked decline in BMD (Partial correlation () = -0.47,  < .05) as did high baseline cortisol levels ( = -0.49,  < .05). Malnutrition in liver cirrhosis seems to be associated with osteopenia/osteoporosis, and systemic inflammation (higher TNF-α) and systemic stress (higher cortisol) to bone loss in patients who undergo LT.
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http://dx.doi.org/10.1080/00365521.2020.1735507DOI Listing
March 2020

An international, multi-institution survey of the use of EUS in the diagnosis of pancreatic cystic lesions.

Endosc Ultrasound 2019 Nov-Dec;8(6):418-427

Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.

Background And Objectives: Currently, pancreatic cystic lesions (PCLs) are recognized with increasing frequency and have become a more common finding in clinical practice. EUS is challenging in the diagnosis of PCLs and evidence-based decisions are lacking in its application. This study aimed to develop strong recommendations for the use of EUS in the diagnosis of PCLs, based on the experience of experts in the field.

Methods: A survey regarding the practice of EUS in the evaluation of PCLs was drafted by the committee member of the International Society of EUS Task Force (ISEUS-TF). It was disseminated to experts of EUS who were also members of the ISEUS-TF. In some cases, percentage agreement with some statements was calculated; in others, the options with the greatest numbers of responses were summarized.

Results: Fifteen questions were extracted and disseminated among 60 experts for the survey. Fifty-three experts completed the survey within the specified time frame. The average volume of EUS cases at the experts' institutions is 988.5 cases per year.

Conclusion: Despite the limitations of EUS alone in the morphologic diagnosis of PCLs, the results of the survey indicate that EUS-guided fine-needle aspiration is widely expected to become a more valuable method.
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http://dx.doi.org/10.4103/eus.eus_61_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927137PMC
September 2019

DNA sequencing of cytopathologically inconclusive EUS-FNA from solid pancreatic lesions suspicious for malignancy confirms EUS diagnosis.

Endosc Ultrasound 2020 Jan-Feb;9(1):37-44

Division of Endoscopy, Gastro Unit, Copenhagen University Hospital, Herlev, Denmark.

Background And Objectives: EUS-FNA is inconclusive in up to 10%-15% of patients with solid pancreatic lesions (SPLs). We aimed to investigate whether supplementary genetic analyses with whole-exome sequencing add diagnostic value in patients with SPLs suspicious of malignancy but inconclusive EUS-FNA.

Patients And Methods: Thirty-nine patients, who underwent EUS-FNA of an SPL were retrospectively included. Three groups were defined: 16 (41.0%) had suspected malignancy on EUS confirmed by cytology (malignant), 13 (33.3%) had suspected malignancy on EUS but benign cytology (inconclusive), and 10 (25.6%) had benign EUS imaging and cytology (benign). Areas with the highest epithelial cell concentrations were macro-dissected from the FNA smears from each patient, and extracted DNA was used for whole-exome sequencing by next-generation sequencing of a selected gene panel including 19 genes commonly mutated in cancer.

Results: Pathogenic mutations in K-RAS, TP53, and PIK3CA differed significantly between the three groups (P < 0.001, P = 0.018, and P = 0.026, respectively). Pathogenic mutations in KRAS and TP53 were predominant in the inconclusive (54% and 31%, respectively) and malignant groups (81.3% and 50%, respectively) compared to the benign group (0%). Malignant and inconclusive diagnoses correlated strongly with poor overall survival (P < 0.001).

Conclusion: Whole-exome sequencing of genes commonly mutated in pancreatic cancer may be an important adjunct in patients with SPLs suspicious for malignancy on EUS but with uncertain cytological diagnosis.
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http://dx.doi.org/10.4103/eus.eus_36_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7038737PMC
September 2019

Pancreatic calcifications associate with diverse aetiological risk factors in patients with chronic pancreatitis: A multicentre study of 1500 cases.

Pancreatology 2019 Oct 21;19(7):922-928. Epub 2019 Aug 21.

Clinical Institute, Aalborg University, Aalborg, Denmark; Department of Radiology, Aalborg University Hospital, Aalborg, Denmark.

Background: Pancreatic calcifications is a common finding in patients with chronic pancreatitis (CP), but the underlying pathophysiology is incompletely understood. Past studies for risk factors of calcifications have generally been focused on single parameters or limited by small sample sizes. The aim of this study was to explore several patient and disease characteristics and their associations with pancreatic calcifications in a large cohort of CP patients with diverse aetiological risk factors.

Methods: This was a multicentre, cross-sectional study including 1509 patients with CP. Patient and disease characteristics were compared for patients with calcifications (n = 912) vs. without calcifications (n = 597). Multivariable logistic regression was performed to assess the parameters independently associated with calcifications.

Results: The mean age of patients was 53.9 ± 14.5 years and 1006 (67%) were men. The prevalence of calcifications was 60.4% in the overall patient cohort, but highly variable between patients with different aetiological risk factors (range: 2-69%). On multivariate analysis, alcoholic aetiology (OR 1.76 [95% CI, 1.39-2.24]; p < 0.001) and smoking aetiology (OR 1.77 [95% CI, 1.39-2.26], p < 0.001) were positively associated with the presence of calcifications, while an autoimmune aetiology was negatively associated with calcifications (OR 0.15 [95% CI, 0.08-0.27], p < 0.001). Patients with pancreatic calcifications were more likely to have undergone pancreatic duct stenting (OR 1.59 [95%CI, 1.16-2.19], p = 0.004).

Conclusion: The presence of pancreatic calcifications is associated with diverse aetiological risk factors in patients with CP. This observation attest to the understanding of CP as a complex disease and may have implications for disease classification.
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http://dx.doi.org/10.1016/j.pan.2019.08.009DOI Listing
October 2019

SEMS and Sensibility: Self-Expandable Metal Stents for Malignant Biliary Obstruction-Are Stent Characteristics Important?

Dig Dis Sci 2019 09;64(9):2376-2378

Digestive Disease Center, Copenhagen University Hospital, Herlev, Denmark.

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http://dx.doi.org/10.1007/s10620-019-05742-zDOI Listing
September 2019

Association of multiple patient and disease characteristics with the presence and type of pain in chronic pancreatitis.

J Gastroenterol Hepatol 2020 Feb 31;35(2):326-333. Epub 2019 Jul 31.

Centre for Pancreatic Diseases, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark.

Background And Aim: Pain is the primary symptom of chronic pancreatitis (CP) and associates with a number of patient and disease characteristics. However, the complex interrelations of these parameters are incompletely understood, and pain treatment remains unsatisfactory in a large proportion of patients. The aim of this study is to investigate multiple pain risk factors in a large population of CP patients, with a special emphasis on patients' patterns of smoking and alcohol use.

Methods: This was a multicenter, cross-sectional study including 1384 patients with CP. Patient demographics and disease characteristics, as well as current patterns of smoking and alcohol use, were compared for patients with pain (n = 801) versus without pain (n = 583). Multivariate logistic regression models were performed to assess the variables associated with the presence and type of pain (constant vs intermittent pain).

Results: The mean age of participants was 52.1 ± 14.6 years, and 914 (66%) were men. Active smoking (odds ratio 1.6 [95% confidence interval 1.1-2.2], P = 0.005) and alcohol consumption (odds ratio 1.8 [95% confidence interval 1.1-3.0], P = 0.03) were independently associated with the presence of pain. In addition, patients' age at diagnosis, pancreatic duct pathology, and the presence of pseudocysts, duodenal stenosis, and exocrine pancreatic insufficiency were confirmed as pain risk factors (all P ≤ 0.01). Constant pain, as opposed to intermittent pain, was more frequently reported by smokers (P = 0.03), while alcohol consumption was associated with intermittent pain (P = 0.006).

Conclusion: Multiple patient and disease characteristics, including patterns of smoking and alcohol consumption, associate with the presence and type of pain in patients with CP.
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http://dx.doi.org/10.1111/jgh.14783DOI Listing
February 2020

Next-generation sequencing of endoscopic ultrasound guided microbiopsies from pancreatic cystic neoplasms.

Histopathology 2019 Nov 6;75(5):767-771. Epub 2019 Sep 6.

Department of Pathology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.

Aims: Interpretation of cytology samples from pancreatic cysts is challenging. A novel microbiopsy forceps used during endoscopic ultrasound examinations offers new opportunities for histological examination of tissue from pancreatic cysts as well as next-generation sequencing. The aim of this study was to analyse the results of next-generation sequencing of microbiopsies from pancreatic cysts.

Methods And Results: Microbiopsies from 27 patients were obtained, 23 of which were subjected to next-generation sequencing. Sixteen intraductal papillary mucinous neoplasms harboured mutations in genes regulating cell cycle and repair, and three were without mutations. Most frequent mutations were found in the KRAS and GNAS genes, and these were often concomitant. Three serous cystic neoplasms were without mutations, while with regard to histology, a non-diagnostic microbiopsy harboured a KRAS and a TP53 mutation and was deemed malignant after clinical follow-up. Three patients underwent surgery, and the point mutations detected in the microbiopsies were confirmed in the resected specimens. We identified one resected sample with an additional GNAS mutation which was not identified in the microbiopsy.

Conclusions: Next-generation sequencing of microbiopsies may have the potential to improve diagnostic decision-making.
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http://dx.doi.org/10.1111/his.13949DOI Listing
November 2019

[Diagnostic investigation, treatment and follow-up of pancreatic cysts].

Ugeskr Laeger 2019 Jun;181(23)

Pancreatic cancer has a low five-year survival rate, which in part is due to late recognition of the disease making surgical intervention impossible. Some pancreatic cancers stem from cystic lesions. The expanded use of advanced diagnostic imaging like CT and MRI has led to an increase in incidental and potentially malignant pancreatic cysts. This review presents the newest international guidelines and gives a Danish perspective in order to increase knowledge on how to deal with incidental pancreatic cysts as regards further diagnostic investigation, treatment and follow-up.
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June 2019

Chronic Pancreatitis Is Characterized by Distinct Complication Clusters That Associate With Etiological Risk Factors.

Am J Gastroenterol 2019 04;114(4):656-664

Centre for Pancreatic Diseases, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark.

Objectives: Chronic pancreatitis (CP) is characterized by several disease-related complications and multiple etiological risk factors. Past studies of associations between complications and risk factors have mostly been limited to single complications or highly focused on single etiologies. Using an objective data-driven approach (cluster analysis), we characterized complication clusters and their associations with etiological risk factors in a large cohort of patients with CP.

Methods: This was a multicenter, cross-sectional study including 1,071 patients with CP from the Scandinavian and Baltic countries. Complications to CP were classified according to the M-ANNHEIM system, and treelet transform was used to derive complication clusters. Cluster complication frequencies were analyzed for their association with main etiological risk factors (smoking and alcohol).

Results: The mean age of participants was 57 years and 66% were men. Alcohol (55%) and smoking (53%) were the most common etiological risk factors and seen in combination in 36% of patients. Cluster analysis identified 3 distinct complication clusters characterized by inflammation, fibrosis, and pancreatic insufficiencies. An independent association between inflammatory complications and alcoholic etiology was seen (odds ratio [OR] 2.00 [95% CI [confidence interval], 1.38-2.90], P < 0.001), whereas smoking was associated with fibrosis-related complications (OR 2.23 [95% CI, 1.56-2.3.20], P < 0.001) and pancreatic insufficiencies (OR 1.42 [95% CI, 1.00-2.01], P = 0.046).

Discussion: Three distinctive clusters of complications to CP were identified. Their differing associations with alcoholic and smoking etiology indicate distinct underlying disease mechanisms.
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http://dx.doi.org/10.14309/ajg.0000000000000147DOI Listing
April 2019

Risk factors for chronic and recurrent pancreatitis after first attack of acute pancreatitis.

Scand J Gastroenterol 2019 Jan 31;54(1):87-94. Epub 2019 Jan 31.

a Faculty of Medicine , University of Iceland , Reykjavík , Iceland.

Objective: To study the outcome of acute pancreatitis and risk factors for recurrent and chronic pancreatitis in a population based cohort of patients with first-time acute pancreatitis.

Methods: All patients with first-time acute pancreatitis from 2006-2015 in Iceland were retrospectively evaluated. Medical records were scrutinized and relevant data extracted.

Results: 1102 cases of first-time acute pancreatitis were identified: mean age 56yr, 46% female, 41% biliary, 21% alcohol, 26% idiopathic, 13% other causes, mean follow-up 4yr. 21% had ≥1 recurrent acute pancreatitis which was independently related to alcoholic (vs. biliary hazard ratio (HR) 2.29, 95% confidence interval (CI) 1.51-3.46), male gender (HR 1.48, 95%CI 1.08-2.04), and smoking (HR 1.62, 95%CI 1.15-2.28). 3.7% developed chronic pancreatitis. Independent predictors were recurrent acute pancreatitis (HR 8.79, 95%CI 3.94-19.62), alcoholic (vs. biliary HR 9.16, 95%CI 2.71-30.9), local complications (HR 4.77, 95%CI 1.93-11.79), and organ-failure (HR 2.86, 95%CI 1.10-7.42).

Conclusions: Recurrent acute pancreatitis occurred in one-fifth of patients. Development of chronic pancreatitis was infrequent. Both recurrent acute pancreatitis and chronic pancreatitis were related to alcoholic acute pancreatitis, while recurrent acute pancreatitis was associated with smoking and male gender, and chronic pancreatitis to recurrent acute pancreatitis, organ-failure, and local complications.
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http://dx.doi.org/10.1080/00365521.2018.1550670DOI Listing
January 2019

Subtyping of intraductal papillary mucinous neoplasms - pitfalls of MUC1 immunohistochemistry.

APMIS 2019 Jan 22;127(1):27-32. Epub 2018 Nov 22.

Department of Pathology, Copenhagen University Hospital Rigshospitalet, København, Denmark.

Intraductal papillary mucinous neoplasms (IPMNs) are precursor lesions of pancreatic ductal adenocarcinoma (PDAC). Current edition of WHO Classification of Tumors of the Digestive System recognizes four different subtypes (gastric, intestinal, pancreatobiliary, and oncocytic) and recommends analysis of mucin expression (MUC1, MUC2, MUC5AC, MUC6) as well as evaluation of architectural and cell differentiation patterns for correct classification. However, there is no consensus on MUC1 expression of IPMN-lesions in the literature. Current recommendations are based on studies where antibodies against the core MUC1 protein or sialylated MUC1 (tumor associated MUC1), not the fully glycosylated MUC1 were used. We have recently reported that MUC1 is strongly expressed in both gastric and intestinal types IPMN specimens from the cystic wall, obtained by endoscopic ultrasound guided microbiopsy procedure. We have used a commercial MUC1 antibody, validated and recommended for diagnostic use, which recognizes fully glycosylated MUC1. Based on the above, we propose a revision of the WHO Classification, specifying that antibodies against tumor associated MUC1 should be used for IPMN subtyping.
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http://dx.doi.org/10.1111/apm.12900DOI Listing
January 2019

A multi-institution consensus on how to perform EUS-guided biliary drainage for malignant biliary obstruction.

Endosc Ultrasound 2018 Nov-Dec;7(6):356-365

Department of Endoscopy, Yokohama City University School of Medicine, Yokohama, Japan.

Background And Objectives: EUS-guided biliary drainage (EUS-BD) was shown to be useful for malignant biliary obstruction (MBO). However, there is lack of consensus on how EUS-BD should be performed.

Methods: This was a worldwide multi-institutional survey among members of the International Society of EUS conducted in February 2018. The survey consisted of 10 questions related to the practice of EUS-BD.

Results: Forty-six endoscopists of them completed the survey. The majority of endoscopists felt that EUS-BD could replace percutaneous transhepatic biliary drainage after failure of ERCP. Among all EUS-BD methods, the rendezvous stenting technique should be the first choice. Self-expandable metal stents (SEMSs) were recommended by most endoscopists. For EUS-guided hepaticogastrostomy (HGS), superiority of partially-covered SEMS over fully-covered SEMS was not in agreement. 6-Fr cystotomes were recommended for fistula creation. During the HGS approach, longer SEMS (8 or 10 cm) was recommended. During the choledochoduodenostomy approach, 6-cm SEMS was recommended. During the intrahepatic (IH) approach, the IH segment 3 was recommended.

Conclusion: This is the first worldwide survey on the practice of EUS-BD for MBO. There were wide variations in practice, and randomized studies are urgently needed to establish the best approach for the management of this condition.
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http://dx.doi.org/10.4103/eus.eus_53_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6289007PMC
December 2018

Initial experience with EUS-guided microbiopsy forceps in diagnosing pancreatic cystic lesions: A multicenter feasibility study (with video).

Endosc Ultrasound 2018 Nov-Dec;7(6):383-388

Division of Endoscopy, Gastro Unit, Copenhagen University Hospital Herlev, Copenhagen, Denmark.

Background And Objectives: Cystic lesions of the pancreas represent a diagnostic dilemma. Recently, a through-the-needle microbiopsy forceps has become available, enabling procurement of EUS-guided histological specimens from the pancreatic cyst wall. The aim of this study was to evaluate the use of this novel instrument in a multicenter clinical setting.

Patients And Methods: Patients referred for EUS evaluation of pancreatic cysts and attempted EUS-guided microbiopsy was included retrospectively from six international tertiary centers. Patient's demographics, EUS findings, technical and clinical success, and histopathological results were recorded.

Results: : A total of 28 patients were identified. We report a technical success rate of 85.7% (n = 24). Biopsies were generally of good quality and contributed to the diagnosis in 20 patients (clinical success of 71.4%). Three adverse events were recorded (10.7%).

Conclusions: The use of the microbiopsy forceps is feasible with acceptable rates of technical and clinical success. Prospective studies are warranted to determine the diagnostic potential compared to the other modalities. However, the results from this preliminary study are promising.
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http://dx.doi.org/10.4103/eus.eus_16_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6289018PMC
September 2018

Diagnosis of intraductal papillary mucinous neoplasm using endoscopic ultrasound guided microbiopsies: A case report.

World J Gastrointest Endosc 2018 Jul;10(7):125-129

Gastro Unit, Division of Endoscopy, Copenhagen University Hospital Herlev and Gentofte, Herlev 2730, Denmark.

Pancreatic cysts are increasingly diagnosed due to expanding use of cross-sectional imaging, but current diagnostic modalities have limited diagnostic accuracy. Recently, a novel through-the-needle microbiopsy forceps has become available, offering the possibility of obtaining cyst-wall biopsies. We present a case of 41-year-old male with chronic pancreatitis and a 2-cm pancreatic cyst, initially considered a pseudocyst. Subsequently, endoscopic ultrasound guided microbiopsies were successfully obtained, which surprisingly revealed an intraductal papillary mucinous neoplasm of mixed subtype with low grade dysplasia. In conclusion, obtaining biopsies from the wall of the pancreatic cystic lesions with this novel instrument is feasible and, as demonstrated in this case, can possibly alter the clinical outcome. Microbiopsies offered enough cellular material, allowing supplemental gene mutation analysis, which combined with other modalities could lead to a more individual approach when treating pancreatic cysts. However, prospective studies are warranted before routine clinical implementation.
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http://dx.doi.org/10.4253/wjge.v10.i7.125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6068726PMC
July 2018
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